The U.S. Food and Drug Administration sets guidelines for electronic regulatory submissions for the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER).

The agency has long relied upon PDF because of Acrobat’s ability to faithfully render all aspects of printed pages including layout, tables, images and fonts (typefaces).

Font Substitution
Acrobat renders—on the fly—a “faux font” representation using typeface information included in the PDF.

Font Subsetting
Only the typeface characters necessary to render the file are embedded. Typefaces may have thousands of characters. Only embedding the actual characters used can reduce file size.

Font Embedding
All typefaces necessary to render a font are embedded in the file.

While Font Substitution keeps file sizes small, it can be problematic for submissions as non-standard fonts and specialized math symbols may not render faithfully for reviewers.

Font Subsetting is a tempting choice because it renders all the characters in a document accurately while keeping file size to a minimum. However, subsetting can result in “file bloat” if you regularly combine files. The Acrobat Distiller Reference Manual discusses this issue:

When Acrobat merges two PDF files, each containing a subsetted version of the same font, it produces a new PDF file that retains both subsetted fonts. The net size of the two subsetted fonts may be larger than the full font would have been.

Unfortunately, the “Standard” conversion setting in Acrobat does not embed the most common office fonts. These fonts such as Arial and Times Roman are normally installed as part of the operating system.

A recommended best practice is to create a new PDF Conversion setting which embeds all fonts and use it for creating all PDFs.